Julijana Kristl
University of Ljubljana, Faculty of Pharmacy, Faculty Member
Electrospinning is a unique and versatile technique for the fabrication of nanofibers that mimics the native extracellular matrix for tissue engineering. In this paper, hydroxyethyl cellulose (HEC) has been electrospun. Selected... more
Electrospinning is a unique and versatile technique for the fabrication of nanofibers that mimics the native extracellular matrix for tissue engineering. In this paper, hydroxyethyl cellulose (HEC) has been electrospun. Selected parameters of spinning solutions (viscosity, conductivity and surface tension) and process parameters (applied voltage, needle-to-collector distance and collector type) were studied. The formation of nanofibers was found to depend absolutely on the right combination of voltage and distance. HEC concentration was varied from 0.25 to 2.0 % (w/w) and various additives – Tween 80, sodium chloride and organic solvents – were tested. SEM micrographs showed that HEC nanofibers with large numbers of beads could be reduced by addition of Tween 80 and sodium chloride. Addition of organic solvents did not improve nanofiber formation. It was shown that the key solution properties influencing nanofiber morphology were the polymer concentration, the viscosity and surface tension of its solution. Additionally, there are no methods or procedures for electrospinning that are universally applicable. Each polymer needs to be studied individually and the respective electrospinning conditions determined experimentally. Understanding the process and solution properties influencing the electrospun fibers is helpful in the design of tissue scaffolds. HEC nanofibers could offer advantages in the development of modern wound dressings.
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Research Interests: Chemistry, Flow Cytometry, Nanoparticle, Cell Cycle, Nanoparticles, and 15 moreMitochondria, Nanotechnology, Medicine, Humans, Magnetic nanoparticles, Iron Oxide, Iron Oxide Nanoparticles, Magnetic Fields, Magnetic Nanoparticles, Drug Carriers, Lactic Acid, Cytoplasm, Endosomes, Magnetite Nanoparticles, and Cell culture techniques
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Research Interests: Chemical Engineering, Algorithms, Chemistry, Water, Calcium, and 15 moreHydrogels, Medicine, Polymer, Controlled release, Viscosity, Xanthan Gum, Swelling, Tablets, Ionic Strength, Excipients, Drug Release, Physical Properties, Pentoxifylline, Pharmaceutical preparations, and Pharmacology and pharmaceutical sciences
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Research Interests: Chemistry, Chromatography, Scanning Electron Microscopy, Powder Diffraction, Nanoparticles, and 15 morePharmaceutical Chemistry, Medicine, Pharmaceutics, Dissolution, Particle Size, Freeze Drying, Emulsions, Powders, Emulsion, Excipients, Drug Compounding, Biological Availability, Meloxicam, Isoelectric point, and Pharmacology and pharmaceutical sciences
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Sunscreens containing ZnO and TiO2 nanoparticles (NPs) are increasingly applied to skin over long time periods to reduce the risk of skin cancer. However, long‐term toxicological studies of NPs are very sparse. The in vitro toxicity of... more
Sunscreens containing ZnO and TiO2 nanoparticles (NPs) are increasingly applied to skin over long time periods to reduce the risk of skin cancer. However, long‐term toxicological studies of NPs are very sparse. The in vitro toxicity of ZnO and TiO2 NPs on keratinocytes over short‐ and long‐term applications is reported. The effects studied are intracellular formation of radicals, alterations in cell morphology, mitochondrial activity, and cell‐cycle distribution. Cellular response depends on the type of NP, concentration, and exposure time. ZnO NPs have more pronounced adverse effects on keratinocytes than TiO2. TiO2 has no effect on cell viability up to 100 μg mL−1, whereas ZnO reduces viability above 15 μg mL−1 after short‐term exposure. Prolonged exposure to ZnO NPs at 10 μg mL−1 results in decreased mitochondrial activity, loss of normal cell morphology, and disturbances in cell‐cycle distribution. From this point of view TiO2 has no harmful effect. More nanotubular intercellular structures are observed in keratinocytes exposed to either type of NP than in untreated cells. This observation may indicate cellular transformation from normal to tumor cells due to NP treatment. Transmission electron microscopy images show NPs in vesicles within the cell cytoplasm, particularly in early and late endosomes and amphisomes. Contrary to insoluble TiO2, partially soluble ZnO stimulates generation of reactive oxygen species to swamp the cell redox defense system thus initiating the death processes, seen also in cell‐cycle distribution and fluorescence imaging. Long‐term exposure to NPs has adverse effects on human keratinocytes in vitro, which indicates a potential health risk.
Research Interests: Biophysics, Materials Science, Cell Cycle, Scanning Electron Microscopy, Titanium, and 15 moreNanoparticles, Transmission Electron Microscopy, Mitochondria, Medicine, Multidisciplinary, Zinc Oxide, Humans, Keratinocytes, Reactive Oxygen Species, Cell, Small, Cell Survival, Cytoplasm, Viability assay, and Intracellular
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Systems for storage and distribution of purified water at ambient temperature are highly susceptible to microbial contamination. The water flow, microbial content and chemical quality of the purified water in an industrial water system... more
Systems for storage and distribution of purified water at ambient temperature are highly susceptible to microbial contamination. The water flow, microbial content and chemical quality of the purified water in an industrial water system have been simulated in a biofilm annular reactor (BAR) to study the impact of different hydrodynamic conditions on biofilm development. Our results reveal the potential of stagnant purified water at total organic compounds (TOC) below 50ppb to develop biofilm that allows detachment of planktonic bacteria and colonization of new surfaces within 24h. However, under constant water flow over 7 days, the growth of initial biofilm was 40 times less, fewer bacteria were detached, and new surfaces were colonized to a lesser extent. Heterotrophic plate counts (HPCs) in biofilm were highly positively correlated with numbers of detached planktonic bacteria in effluent water. The study shows that the hydrodynamic conditions and level of planktonic HPC in water are critical for the development of biofilm at very low TOC. The results in the BAR agreed well with those from regular industrial microbial monitoring of purified water. To conclude, the BAR successfully simulates biofilm growth and can be used to establish an effective biofilm control strategy. However, the microbial quality of purified water in industrial system is a constant challenge; any increase of HPC in effluent water is a sign to take steps against excessive microbial growth.
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Research Interests: Chemistry, Water, Nuclear Magnetic Resonance, NMR Spectroscopy, Polymers, and 15 moreHydrogels, Medicine, Cellulose, Adsorption, Polymer, Room Temperature, Ether, Molecular Mass, AAPS PharmSciTech, Delayed-Action Preparations, Protons, Ethers, Substituent Effect, Relaxation Time, and Pharmacology and pharmaceutical sciences
Mucus is a viscoelastic gel covering the entire alimentary tract. It represents a pre-epithelial diffusion barrier influencing the drug absorption process. In this way the rheological properties of mucus play an important role. The... more
Mucus is a viscoelastic gel covering the entire alimentary tract. It represents a pre-epithelial diffusion barrier influencing the drug absorption process. In this way the rheological properties of mucus play an important role. The purpose of our investigation was to evaluate and compare the rheological properties of rehydrated dried crude porcine gastric mucin (Sigma mucin) and isolated natural porcine gastric mucus. Two different rheological approaches were used: constant shear and oscillatory shear conditions. The results obtained under steady shear conditions show that the reduction of apparent viscosity is caused by time, shear rate and temperature. With increasing Sigma mucin concentration the rheological behaviour changes from time-independent systems fitting in with the Casson model to time-dependent systems fitting in with the Herschel-Bulkley rheological model. Measurements performed under oscillatory shear conditions clearly show how the mechanical response of different concentrated systems has changed from dispersions with prevailing plastic to prevailing elastic properties. Mechanical deformation and frequency response of natural gastric porcine mucus have shown a strong gel structure with elastic properties. Comparing both systems it can be concluded that after rehydration of dried crude gastric porcine mucin, a model mucus system with rheological properties equivalent to natural mucus cannot be obtained.
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The main goal of this study was to present general performances of AFM in investigations of different properties of pharmaceutical materials such as conformational structure of polymer molecules, particle characterization including size... more
The main goal of this study was to present general performances of AFM in investigations of different properties of pharmaceutical materials such as conformational structure of polymer molecules, particle characterization including size and shape, and morphological properties (surface roughness analysis). AFM is a precise and versatile technique for investigation of conformational structures of polymer molecules, which might be possible reason for variable swelling capability and release properties of xanthan, as drug delivery controlled agent. Furthermore, tapping mode AFM could be suitable scan method for nanoparticles characterization such as size, shape and roughness.
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Research Interests: Andrology, Senescence, Biology, In Vitro, RM, and 5 moreIn Vivo, Farmacia, Fibroblast, Trypan Blue, and Ageing
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The development of formulations, which increase skin oxygenation and of methods for measuring oxygen levels in skin are important for dealing with processes affected by the level of oxygen, e.g., rate of healing and efficiency of... more
The development of formulations, which increase skin oxygenation and of methods for measuring oxygen levels in skin are important for dealing with processes affected by the level of oxygen, e.g., rate of healing and efficiency of radiation oncology. In this study we have investigated the role of carriers on the efficacy of benzyl nicotinate (BN) action in skin after dermal application in different formulations by EPR oximetry in vivo. The time course of pO2 in the skin after application of rubefacient is followed directly for the first time. The results obtained proved the applicability of in vivo EPR oximetry as a sensitive method by which small alterations in pO2 can be detected. We have found that the type of vehicle significantly influences the time when BN starts to act, the duration of its action, and the maximal increase in pO2. The ranking of vehicle efficiency was: lipid nanoparticles in hydrophilic gel>liposomes in hydrophilic gel>hydrophilic gel>hydrophobic ointment>hydrophobic cream. Primarily the semi-solid vehicle determines the lag-time of action, but the maximal oxygen level is influenced decisively by the particulate carrier systems. BN effectiveness was dose dependent. 2.5% w/w concentration of BN appears to be the most appropriate for therapeutic application. After repeated application a successive increase of pO2 base line in skin and of the maximal pO2 was noticed.
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Research Interests: Biophysics, Chemistry, Cytotoxicity, Medicine, Pharmaceutics, and 15 moreLipids, Cell line, Humans, Antioxidant, Liposomes, Liposome, Epithelial cells, Particle Size, Cell Shape, Cell Proliferation, Drug Compounding, Drug Stability, Cell Survival, Intracellular, and Pharmacology and pharmaceutical sciences
Research Interests: Chemistry, Nanoparticle, Nanotechnology, Medicine, DISTRIBUTION, and 12 moreLipids, Dispersion, Pharmaceutical Sciences, Solid Lipid Nanoparticles, Liposome, Partition Coefficient, Lipophilicity, Distribution, Microspheres, Electron Paramagnetic Resonance, Poloxamer, and Pharmacology and pharmaceutical sciences
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Orlistat is locally acting inhibitor of gastrointestinal lipases which has been developed for the treatment of obesity. The present study was designed with the intent to formulate orlistat in a different way compared to the current... more
Orlistat is locally acting inhibitor of gastrointestinal lipases which has been developed for the treatment of obesity. The present study was designed with the intent to formulate orlistat in a different way compared to the current practice and investigate its inhibition of gastrointestinal lipases. Orlistat is considered as a technologically problematic and unmanageable substance because of waxy nature, low melting point and low chemical stability. The manuscript presents the critical issues regarding engineering of its nanosuspension with controlled particle size by melt emulsification and high pressure homogenization. In order to formulate dry product, lactose was dissolved in nanosuspension as filler and spray drying has been performed for obtaining the final powder product. Laser diffraction, scanning electron microscopy and atomic force microscopy have been used for orlistat nanosuspension characterization, dissolution studies and lipase inhibition studies were performed to characterize the in vitro efficacy of formulated orlistat. The advantage of selected technological procedures is nanosized orlistat with elevated in vitro dissolution rate in comparison to raw drug, physical mixture and marketed product. Furthermore, nanosuspension demonstrated significantly higher in vitro lipase inhibition in comparison to references. To conclude, the results show new technological solution and remarkable increase of pharmacological effect which could potentially lead to decreasing the dose and consequently dose dependent side effects.
Research Interests: Chemistry, High Pressure, Kinetics, Nanoparticle, Pharmaceutical Technology, and 15 moreEnzyme Inhibitors, Nanoparticles, Nanotechnology, Pharmaceutical Chemistry, Atomic Force Microscopy, Medicine, Homogenization, In Vitro, Dissolution, Particle, Lactose, Orlistat, Drug Compounding, Lipase, and Lactones
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The effects of two general anesthetics on skin oxygenation in mice are evaluated by electron paramagnetic resonance oximetry. Up to now no data on the effects of different anesthetics on skin oxygenation could be found. In this study... more
The effects of two general anesthetics on skin oxygenation in mice are evaluated by electron paramagnetic resonance oximetry. Up to now no data on the effects of different anesthetics on skin oxygenation could be found. In this study animals were anesthetized with ketamine/xylazine or isoflurane, and partial pressure of oxygen (pO2) in the skin, heart rate and hemoglobin oxygen saturation were followed as a function of time and inhaled oxygen concentration. The skin pO2 significantly increased continuously for about 60 min in mice anesthetized with isoflurane and remained constant after that. During ketamine/xylazine anesthesia, the pO2 in the skin only slightly decreased. The skin pO2 increased with higher inspired oxygen concentrations for both anesthetics groups. When breathing 21% oxygen, mice anesthetized with isoflurane had two-fold higher pO2 in the skin compared to mice anesthetized with ketamine/xylazine. The heart rate was significantly lower in animals anesthetized with ketamine/xylazine, while hemoglobin saturation was almost the same in both groups at all inhaled oxygen concentrations. These results show that the type of anesthesia is an important parameter that needs to be considered in experiments where skin pO2 is followed.
Research Interests: Chemistry, Medicine, Mice, Female, Animals, and 14 moreKetamine, Anesthesia, Heart rate, Skin, Xylazine, In Vivo, Oxygen, Electron Paramagnetic Resonance Spectroscopy, Isoflurane, Hemoglobins, Electron Paramagnetic Resonance, Oxygen saturation, Oxygenation, and Pharmacology and pharmaceutical sciences
Solid lipid nanoparticles (SLN) have been praised for their advantageous drug delivery properties such as biocompatibility, controlled release and passive drug targeting. However, the cytotoxicity of SLN and their ingredients, especially... more
Solid lipid nanoparticles (SLN) have been praised for their advantageous drug delivery properties such as biocompatibility, controlled release and passive drug targeting. However, the cytotoxicity of SLN and their ingredients, especially over a longer time period, has not been investigated in detail. We examined the critical issues regarding the use of a surface active stabilizer Tyloxapol (Tyl) for the preparation of solid lipid particles (SLP) and their effects on cellular functions and viability. SLP composed of behenate, phospholipids and a stabilizer, Tyloxapol or Lutrol (Lut), were prepared by the lipid melt method, labeled with a fluorescent dye and tested on Jurkat or HEK293 cells. The nano-sized particles were rapidly internalized and exhibited cytoplasmic localization. Incubation of cells with SLP-Tyl resulted in a dose- and time-dependent cytostatic effect, and also caused moderate and delayed cytotoxicity. Tyloxapol solution or SLP-Tyl dispersion caused the detachment of HEK293 cells, a decrease in cell proliferation and alterations in cellular morphology. Cell cycle analysis revealed that, while the unfavourable effects of SLP-Tyl and Tyloxapol solution are similar initially, longer incubation results in partial recovery of cells incubated with the dispersion of SLP-Tyl, whereas the presence of Tyloxapol solution induces apoptotic cell death. These findings indicate that Tyloxapol is an unfavourable stabilizer of SLP used for intracellular delivery and reinforce the role of stabilizers in a design of SLP with minimal cytotoxic properties.
Research Interests: Biophysics, Chemistry, Cell Cycle, Drug delivery, Cytotoxicity, and 15 moreApoptosis, Medicine, Cell line, Humans, Controlled release, Cell Death, Colloids, Solid Lipid Nanoparticles, Particle Size, Surface Active Agents, Cell Proliferation, Drug Targeting, Cell Survival, Polyethylene Glycols, and Pharmacology and pharmaceutical sciences
Research Interests: Chemistry, Free Radicals, Fluorescence Microscopy, Cytotoxicity, Free Radical, and 15 moreAntioxidants, Cell line, In Vitro, Humans, Antioxidant, Liposomes, Liposome, Antioxidant Activity, Cell Shape, Indexation, Cell Proliferation, Drug Compounding, Cell Survival, Antioxidant Capacity, and Electron Paramagnetic Resonance
Poorly water-soluble compounds are difficult to develop as drug products using conventional formulation techniques and are frequently abandoned early in discovery. In the present study, the melt emulsification method traditionally used to... more
Poorly water-soluble compounds are difficult to develop as drug products using conventional formulation techniques and are frequently abandoned early in discovery. In the present study, the melt emulsification method traditionally used to prepare solid lipid nanoparticles was adapted to produce drug nanosuspensions. The method was evaluated in comparison with the well known solvent diffusion process for ibuprofen as a model drug. Control of the preparation variables (stabilizers, drug content, homogenization procedure and cooling conditions) allowed formation of nanosuspensions with diameters less than 100 nm. The major advantage of the melt emulsification method over the solvent diffusion method is the avoidance of organic solvents during production, although the mean particle size is slightly greater. The combination of Tween 80 and PVP K25 as stabilizers yields nanosuspensions with the smallest average particle size. The formulation of ibuprofen as a nanosuspension, either in the form of lyophilized powder or granules, was very successful in enhancing dissolution rate, more than 65% of the drug being dissolved in the first 10 min compared to less than 15% of the micronized drug. The increase in in vitro dissolution rate may favourably affect bioavailability and improve safety for the patient by decreasing gastric irritancy.
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ABSTRACT Piroxicam is a highly potent anti-inflammatory and analgetically active drug the bioavailability of which is affected by its low solubility and dissolution rate. To modify its dissolution characteristics, solvent deposits of... more
ABSTRACT Piroxicam is a highly potent anti-inflammatory and analgetically active drug the bioavailability of which is affected by its low solubility and dissolution rate. To modify its dissolution characteristics, solvent deposits of piroxicam and spin-labelled piroxicam (4-hydroxy-2-methyl-N-(1-oxyl-2,2,6,6-tetramethylpiperidin-4-yi)-2 H-1,2-benzothiazine-3-car☐amide 1,1-dioxide) on silica (amorphous non-porous silicon dioxide) or on sodium chloride crystals were prepared.Electron paramagnetic resonance (EPR) spectra reveal the distribution and packing of molecules on the surface of the carriers. For concentration ranges up to 3 · 10−5 mol g−1 silica ( ⩾ 0.06 molecules nm−2) the relative populations of agglomerates and sparingly populated regions were detected, including the possible rearrangement of deposited piroxicam molecules upon heat treatment. The relative dissolution rates conform with the population of the agglomerated fraction of piroxicam.
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... Učinkovitost je odvisna od sposobnosti učinkovine, da (i) preide eno ali več bioloških pregrad (npr. sluznico, epi-tel, endotel), (ii) prehaja v tkiva in nato skozi plazmelemo in (iii) nazadnje doseže organel ali citosol, kjer se... more
... Učinkovitost je odvisna od sposobnosti učinkovine, da (i) preide eno ali več bioloških pregrad (npr. sluznico, epi-tel, endotel), (ii) prehaja v tkiva in nato skozi plazmelemo in (iii) nazadnje doseže organel ali citosol, kjer se nahaja ciljno mesto učinko-vine. ...
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Imunske celice se nahajajo v telesnih tekoeinah in tkivih po celotnem organizmu in predstavljajo premikajoee taree za ciljanje z ueinkovinami. Zaradi neoptimalnega klasioenega naoeina dostavljanja uoeinkovin tem celicam, kjer bi le z... more
Imunske celice se nahajajo v telesnih tekoeinah in tkivih po celotnem organizmu in predstavljajo premikajoee taree za ciljanje z ueinkovinami. Zaradi neoptimalnega klasioenega naoeina dostavljanja uoeinkovin tem celicam, kjer bi le z visokimi vrednostmi proste uoeinkovine v serumu dosegli zadovoljive ueinke, predstavljajo nanodelci privlaeen sistem za dostavo ueinkovin imunskim celicam. Nanodelce lahko uporabimo kot dostavne sisteme za bolj ueinkovit vnos antigenov v antigen predstavitve celice, kot tudi za dostavo uoeinkovin doloeenim populacijam limfocitov. S tem dosezemo regulacijoimunskega delovanja ali pa imunski sistem izkoristimo za poveeanje ueinkovitosti vgrajenih ueinkovin v nanodelce pri zdravljenju okuzenih ali tumorskih celic
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Research Interests: Ultrasound and Medicine
Ascorbic acid and its derivatives are antioxidants and can be used for protecting skin against ultraviolet induced free radicals. In the present work, two ascorbic acid derivatives, hydrophilic sodium ascorbyl phosphate and amphiphilic... more
Ascorbic acid and its derivatives are antioxidants and can be used for protecting skin against ultraviolet induced free radicals. In the present work, two ascorbic acid derivatives, hydrophilic sodium ascorbyl phosphate and amphiphilic ascorbyl palmitate, incorporated in microemulsions as carrier systems for dermal application, have been investigated and compared. Their effectiveness against free radical formation in porcine skin was determined with EPR spectroscopy using a spin trapping technique. Both antioxidants applied to the skin decreased the level of free radical formation. We showed that effectiveness of both derivatives was dependent on their concentration. For sodium ascorbyl phosphate the application time had also a significant influence on its effectiveness, while the effectiveness of ascorbyl palmitate depended primarily on the type of microemulsion.